Distinct patterns of structural and numerical chromosomal instability characterize sporadic ovarian cancer
Distinct patterns of structural and numerical chromosomal instability characterize sporadic ovarian cancer
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DOI：
10.1593/neo.08584
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Squire, Jeremy A.
中科院分区：
文献类型：
--
作者：
Bayani, Jane;Paderova, Jana;Squire, Jeremy A.
散发性卵巢癌是一种特别具有侵袭性的肿瘤，其特征是高度异常的核型，表现出许多基因组不稳定性的特征。肿瘤中更复杂的基因组变化是染色体不稳定性（CIN）的结果，其可产生数值[（N）-CIN]和结构染色体不稳定性[（S）CIN]。在这项研究中，分子细胞遗传学分析用于评估（N）-CIN和（S）-CIN的相对水平。六个肿瘤具有近二倍体染色体数目，两个是近四倍体，两个是近三倍体。（N）-CIN水平作为总体肿瘤基因组含量的函数而增加，其中近二倍体肿瘤表现出7.0至21.0范围内的数值不稳定指数，近四倍体和三倍体肿瘤表现出24.9至54.9范围内的不稳定指数。相比之下，二倍体肿瘤中的（S）-CIN程度通常比近四倍体肿瘤更明显。为了确定相关的染色体组成和/或倍性变化是否受到有丝分裂分离错误的影响，对所有10个肿瘤进行中心体分析。近二倍体肿瘤，具有最低的数值变化，观察到具有较少的中心体异常细胞（5.5%至14.0%），而近四倍体肿瘤具有更高水平的（N）-CIN，其特征在于具有异常中心体的细胞百分比升高的趋势（16.0%至20.5%）。这些观察结果表明，卵巢癌中控制基因组稳定性的两个不同过程可能会被破坏：那些影响染色体数量分离和倍性的过程，以及那些影响DNA修复保真度并导致结构畸变的过程。
Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN), which can generate both numerical [(N)-CIN] and structural chromosomal instability [(S)CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels of both (N)-CIN and (S)-CIN. Six tumors had a near-diploid chromosome number, two were near-tetraploid, and two were near-triploid. (N)-CIN levels increased as a function of overall tumor genomic content, with near-diploid tumors exhibiting numerical instability indices ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S)-CIN was generally more evident in the diploid tumors compared with the near-tetraploid tumors. To determine whether the associated chromosomal constitution and/or ploidy changes were influenced by mitotic segregation errors, centrosome analyses were performed on all 10 tumors. The near-diploid tumors, with the lowest numerical change, were observed to possess fewer cells with centrosome abnormalities (5.5% to 14.0%), whereas the near-tetraploid tumors possessed much higher levels of (N)-CIN and were characterized by a trend of elevating percentages of cells with abnormal centrosomes (16.0% to 20.5%). These observations suggest that two distinct processes governing genome stability may be disrupted in ovarian cancer: those that impact on numerical segregation and ploidy of chromosomes and those that affect the fidelity of DNA repair and lead to structural aberrations.